Abstract
BACKGROUND: Many people worldwide have developed a combination of natural and vaccine-induced immunity to COVID-19. This study investigated whether exposure to SARS-CoV-2 before full vaccination promotes protection against a breakthrough infection. METHODS: We studied a total of 2,902,545 people in the Isfahan COVID-19 Registry. All the participants had received two doses of either Sinopharm BIBP, ChAdOx1-nCoV-19, Gam-COVID-Vac, or BIV1-CovIran vaccines. A cohort study examined the association between prior COVID-19 infection and the risk of a breakthrough infection for each vaccine. Cohorts in each pair were matched by gender, age group, calendar week of the first dose, the interval between the first and second doses, and the proportion of healthcare workers. The probable virus variant for the previous infections was also considered. Each individual's follow-up started 14 days after their second vaccine dose until either the end of the study censoring date, occurrence of a COVID-19 infection, or death. The breakthrough infection risk was compared between each cohort pair by using the hazard ratio (HR) and incidence rate ratio (IRR). RESULTS: Total breakthrough HRs (95% confidence interval) (previously infected over infection-naïve matched cohort) were 0.36 (0.23-0.55), 0.35 (0.32-0.40), 0.37 (0.30-0.46), and 0.43 (0.32-0.56) for the BIV1-CovIran, Sinopharm BIBP, Gam-COVID-Vac, and ChAdOx1-nCoV-19 vaccine groups, respectively. The breakthrough infection IRRs were approximately similar to the total HRs mentioned above. CONCLUSION: Prior SARS-CoV-2 infection conferred additive immunity against breakthrough after vaccination, no matter which vaccine brand was injected. Such a result could guide health authorities to codify low-cost high-benefit vaccination protocols and protect the community's well-being.